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. 2024 Dec 10;25(1):1186.
doi: 10.1186/s12864-024-11077-5.

Unveiling genetic insights: Array-CGH and WES discoveries in a cohort of 122 children with essential autism spectrum disorder

Paola Granata  1 , Alessandra Zito  2 , Dario Cocciadiferro  3 , Antonio Novelli  3 , Chiara Pessina  1 , Tommaso Mazza  3   4 , Matteo Ferri  5 , Paolo Piccinelli  5 , Chiara Luoni  5 , Cristiano Termine  6 , Mauro Fasano  7   8 , Rosario Casalone  1
Affiliations

Unveiling genetic insights: Array-CGH and WES discoveries in a cohort of 122 children with essential autism spectrum disorder

Paola Granata et al. BMC Genomics. .

Abstract

Background: Autistic Spectrum Disorder (ASD) is a neurodevelopmental disorder with a strong genetic component and high heterogeneity. Essential ASD refers to patients who do not have other comorbidities. This study aimed to investigate the genetic basis of essential ASD using whole exome sequencing (WES) and array-comparative genomic hybridization (array-CGH).

Results: In a cohort of 122 children with essential ASD, WES detected 382 variants across 223 genes, while array-CGH identified 46 copy number variants (CNVs). The combined use of WES and array-CGH revealed pathogenic variants in four patients (3.1% detection rate) and likely pathogenic variants in 34 patients (27.8% detection rate). Only one patient had a pathogenic CNV (0.8% detection rate). Including likely pathogenic variants, the overall detection rate was 31.2%. Additionally, 33 de novo heterozygous sequence variants were identified by WES, with three classified as pathogenic and 13 as likely pathogenic. Sequence variants were found in 85 genes already associated with ASD, and 138 genes not previously included in the SFARI dataset were identified as potential new candidate genes.

Conclusions: The study enhances genetic understanding of essential ASD and identifies new candidate genes of interest. The findings suggest that using both array-CGH and WES in patients with essential ASD can improve the detection of pathogenic and likely pathogenic genetic variants, contributing to better diagnosis and potentially guiding future research and treatment strategies.

Keywords: ASD; Array-comparative genomic hybridization (array-CGH); Copy number variants (CNVs); Essential autistic spectrum disorder.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The project was approved by the Ethics Committee of “ASST dei Sette Laghi” hospital in Varese, Italy on 19/12/2017. Informed written consent was obtained from each patient. As regards the participation of children in the research, consent and authorization were signed by the parents in accordance with the rules laid down by the Ethics Committee of “ASST dei Sette Laghi” hospital. Consent for publication: Written informed consent for publication was provided by the parents, for each patient. Competing interests: The authors declare no competing interests.

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